Oncology Letters
·
2018
·Vol. 15
·期 4
·5739-5743
·
IF 1.664
Hua Zhang,Yumei Cao,Yuru Chen,Guangxi Li,Hanshu Yu
The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC‑7721 cells. Expression of the apoptosis-related genes Bcl-2, Bax and caspase-9 after apatinib treatment was detected by reverse transcription‑quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the in vitro proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC‑7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes Bax and caspase-9 and inhibited the expression of anti-apoptotic gene Bcl-2. In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes Bax and caspase-9, and downregulating the expression level of the anti-apoptotic gene Bcl-2.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2016
·
IF 3.055
Keyou Li,Rui Zhou,Wang Wang Jia,Zhe Li,Jiazhou Li,Pengfei Zhang,Tiancun Xiao
Ethnopharmacological relevance: Zanthoxylum bungeanum ( ZB ), a Chinese herb medicine, has been shown to possess a wide range of biological activities including anti-tumor, anti-inflammatory, and anti-microbial activity and has long been used to treat a variety of skin diseases including psoriasis . However, the underlying mechanism of action has not been systematically elucidated. Aim of the study: to analyze the chemical composition of the hydro-distilled Zanthoxylum bungeanum essential oil (ZBEO), and to investigate its anti-proliferative activity on HaCaT cells as well as the underlying anti-psoriasis mechanisms. Materials and methods: The chemical composition of ZBEO was analyzed with gas chromatography coupled to mass spectrometry (GC-MS). HaCaT cells was exposed to different dose of ZBEO added in medium prior to morphologic features analysis as well as cell cycle arrest examination with Flow cytometry. Western blot analysis was employed to estimate the expression level of proteins including caspase-8/9/3, PARP, Bax and Bcl-2. Results: Thirty-nine compounds of the ZBEO were identified GC-MS. ZBEO-treated HaCaT cells showed typical apoptotic morphologic features by DAPI staining assay. The ZBEO significantly inhibited proliferation of HaCaT cells in a dose- and time-dependent manner and induced S phase arrest apoptosis in HaCaT cells. Furthermore, western blot analysis revealed that the ZBEO increased expression of cleaved caspase-8/9/3, PARP, and Bax, decreased Bcl-2 levels. Conclusion: ZBEO inhibits the proliferation of HaCaT cells, resulting from the induction of cellular apoptosis through both intrinsic and extrinsic pathways. ZBEO is a potential candidate that may be considered for development into an anti-psoriasis drug.
研究领域:
药理学
·
皮肤科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 19
·期 1
·375-383
·
IF 1.448
Xiaowei Shen,Jiaqi Lei,Lei Du
The limited efficacy of chemotherapy with Taxol (TAX) and cisplatin (DDP) in triple‑negative breast cancer (TNBC) has prompted the investigation of combined therapies. Previous studies demonstrated that microRNA (miR)‑31‑5p is involved in various biological processes. In the present study, it was hypothesized that the overexpression of miR‑31‑5p may enhance the efficacy of chemotherapy. The expression levels of miR‑31‑5p in the TNBC cell lines MDA‑MB‑231 and MDA‑MB‑468 were measured using reverse transcription‑quantitative PCR following transfection with miR‑31‑5p mimic or inhibitor. A Cell Counting Kit‑8 and flow cytometry assays suggested that the overexpression of miR‑31‑5p inhibited cell proliferation and promoted apoptosis, and these effects were reversed by transfecting a miR‑31‑5p inhibitor into MDA‑MB‑231 and MDA‑MB‑468 cells. Furthermore, the overexpression of miR‑31‑5p increased the sensitivity of cells to chemotherapy, which exhibited an increase in apoptosis and in the expression level of Bax, and a decrease in the expression level of Bcl‑2. Chemotherapy resistance induced by miR‑31‑5p inhibitor could be reversed by inhibiting the AKT signaling pathway in MDA‑MB‑231 and MDA‑MB‑468 cells. In conclusion, the present preclinical results indicated that targeting miR‑31‑5p may enhance the efficacy of TAX‑ and DDP‑mediated chemotherapy in TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 11
·1814
·
IF 2.861
Wenrui Wang,Lingyu Zhang,Tiantian Chen,Wen Guo,Xunxia Bao,Dandan Wang,Baihui Ren,Haifeng Wang,Yu Li,Yueyue Wang,Sulian Chen,Baoding Tang,Qingling Yang,Changjie Chen
In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the Res-SLNs displayed a superior ability in inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells. Western blot analysis revealed that Res-SLNs could promote the ratio of Bax/Bcl-2 but decreased the expression of cyclinD1 and c-Myc. These results indicate that the Res-SLN may have great potential for breast cancer treatment.Keywords:solid lipid nanoparticle;resveratrol;breast cancer;cyclinD1
研究领域:
药理学
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肿瘤学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Man Ding,Xuechen Zhang,Jiangying Shi,Kaili Cui,Ruipeng Yang,Fengming Liu,Shuhua Shan,Ghani Israr,Zhuoyu Li
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion. Quinoa is a dicotyledonous plant, and the quinoa bran is the outer seed coat of quinoa. Functional molecules in plants play an important role in the treatment and alleviation of chronic diseases. In this study, quinoa bran was used as the raw material. The active components with an anti-colorectal cancer effect were extracted by acetone and separated with an AB-8 macroporous resin column, which was further identified as terpenoids by liquid-mass spectrometry (LMS), named Quinoa bran terpenoids (QBT). The yield of quinoa bran terpenoids was 0.77%. Moreover, the results showed that QBT significantly inhibited the proliferation of colorectal cancer cells DLD-1 and HCT-8 with a concentration gradient dependent manner. Respectively, the IC 50 values of DLD-1 and HCT-8 cells were 0.42 ± 0.02 and 0.54 ± 0.05 mg/mL. Further studies showed that QBT upregulated apoptosis-related proteins such as activated-caspase-3, 8, and 9. In addition, QBT decreased mitochondrial membrane potential , promoted the expression of the pro-apoptotic protein Bax, and inhibited the anti-apoptotic protein Bcl-2. The experiments showed that QBT significantly repressed the growth of tumors in nude mice . In conclusion, these results indicated that QBT largely inhibits the development of colorectal cancer to large extent through upregulation of caspase-3, 8, and 9 and reduction of mitochondrial membrane potential, and has great potential for anti-tumor progression.
研究领域:
肿瘤学
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药理学
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植物科学
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产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
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2025
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IF 3.8
Yue Feng,Ying Zhang,Jinxin Li,Junzhe Yu,Yuan Tian,Zunjian Zhang,Fengguo Xu,Pei Zhang
Cisplatin (DDP) is widely utilized in the clinical treatment of malignant tumors, but its effectiveness is significantly compromised by the adverse effects of acute kidney injury (AKI). Renal tubular cells are primarily responsible for DDP-induced AKI (DDP-AKI); however, the responses of heterogeneous renal tubular cells to DDP exposure have not been thoroughly explored. In this study, we employed a targeted metabolomics approach to investigate the metabolic responses of renal tubular cells in DDP-AKI rats. Tubular cells were isolated from the renal cortex and outer medulla, and a chemical derivatization-based liquid chromatography–tandem mass spectrometry (LC–MS/MS) metabolomics method was applied. Our findings revealed distinct metabolic profiles in tubular cells from the renal cortex and outer medulla, with outer medullary cells exhibiting greater sensitivity to DDP exposure. Further analyses identified the tryptophan pathway as a critical factor contributing to these regional differences. Additional functional investigations showed that intermediate metabolites of the tryptophan pathway alleviated DDP cytotoxicity in both cortical and outer medullary tubular cells primarily through modulation of the Bcl2/Bax and Caspase-3 pathway. This study enhances our understanding of the metabolic characteristics of tubular cells across heterogeneous renal regions in DDP-AKI and facilitates further exploration of the underlying mechanisms of DDP-induced nephrotoxicity.
研究领域:
药理学
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肾病学
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代谢组学
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 86
·54369-54378
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IF 3.108
Mengqiao Lian,Yuchao Sun,Yuan Lin,Jin Wen,Marwan Almoiliqy,Bin Xu,Yanli Li,Ming Xu,Dapeng Chen,Zeyao Tang,Li Wang
Catalpol, an iridoid glucoside isolated from the radix of Rehmannia glutinosa Libosch, is found to have a wide variety of biological activities. Based on our pre-experiments, we proposed that catalpol pretreatment could protect against intestinal ischemia/reperfusion (I/R) injury and the JAK2/STAT3 signaling pathway might play an important role in the protection. Both in vivo intestinal I/R-injured rats and in vitro hypoxia/reoxygenation (H/R)-injured IEC-6 cells were used in the present study. The results confirmed our proposal. The in vivo results showed that catalpol (25, 50 mg kg−1) significantly attenuated rat intestinal I/R injury by decreasing pro-inflammatory cytokines, reducing oxidative stress, and restoring intestinal barrier function without affecting the corresponding controls. Catalpol pretreatment significantly increased the Bcl-2/Bax ratio, and decreased cleaved caspase3, p-JAK2, and p-STAT3 protein expression without affecting total JAK2 and STAT3 in vivo and in vitro, showing that catalpol inhibited apoptosis through selectively inhibiting p-JAK2 and p-STAT3. In vitro studies indicated that catalpol (40 μM) pretreatment significantly and selectively inhibited p-STAT3 nuclear translocation and transfection of JAK2 siRNA significantly decreased JAK2, p-JAK2, STAT3, p-STAT3, and other apoptosis-related proteins in H/R-injured IEC-6 cells, suggesting that JAK2 siRNA partially simulated the effects of catalpol on apoptosis-related proteins. JAK2 siRNA + catalpol could not further decrease JAK2, p-JAK2, STAT3, p-STAT3, and other apoptosis-related proteins, suggesting that inhibition of the JAK2/STAT3 signaling pathway plays a key role in catalpol-induced protective effects. Our results suggest that p-JAK2 is the key target in catalpol-induced protection against intestinal I/R injury, providing information for further translational studies.
研究领域:
药理学
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病理生理学
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分子生物学
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产品关联
DOI
高影响因子
Oncology Letters
·
2015
·Vol. 9
·期 4
·1940-1946
·
IF 1.554
Ling Wang,Xianglu Li,Xinyu Liu,Kang Lu,Na Chen,Peipei Li,Xiao Lv,Xin Wang
The aim of the present study was to investigate the indirubin‑enhanced effects of arsenic disulfide (As2S2) on the proliferation and apoptosis of diffuse large B‑cell lymphoma (DLBCL) cells in order to identify an optimum combination therapy. The human DLBCL cells, LY1 and LY8, were treated with different concentrations of indirubin for 24, 48 and 72 h. Next, the cells were treated with 10 µM As2S2 or a combination of 10 µM As2S2 and 20 µM indirubin for 48 h. Cell proliferation inhibition was detected using cell counting kit‑8 and cell apoptosis was determined using flow cytometry. The expression levels of Bcl‑2, Bcl‑2‑associated X protein (Bax) and caspase‑3 were analyzed by quantitative polymerase chain reaction (qPCR) and western blotting. The DLBCL cell viability exhibited no significant changes at 24, 48 or 72 h with increasing indirubin concentration. In addition, the apoptotic rates of the LY1 and LY8 cells demonstrated no noticeable effects at 48 h with increasing indirubin concentration. Following treatment with the combination of indirubin and As2S2, the inhibitory and apoptotic rates of the cells were notably increased compared with those of the As2S2‑treated group. The qPCR results revealed that indirubin alone had no enhancing effect upon the Bax/Bcl‑2 mRNA expression ratio and caspase-3 mRNA expression. Western blot analysis revealed that indirubin alone had an enhancing effect upon the Bax/Bcl‑2 protein ratio and procaspase‑3 protein expression. In addition, the results demonstrated that the 21‑KDa Bax protein was proteolytically cleaved into an 18‑KDa Bax in the DLBCL cells treated with the combination of indirubin and As2S2. Indirubin alone did not inhibit proliferation or induce the apoptosis of the LY1 and LY8 cells. However, the combination of indirubin and As2S2 yielded enhancing effects. Therefore, the results of the present study demonstrated that with regard to antitumor activities, As2S2 served as the principal drug, whereas indirubin served as the adjuvant drug. The enhancing effect was due, in part, to the induction of the mitochondrial apoptotic pathway, which involves the cleavage of Bax.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2021
·Vol. 25
·期 2
·1-9
·
IF 2.952
Fa-Xiu Chen,Qin Wan,Qing-Ling Li,Jing Fang,Le Peng,Jian Hu
The function of substance P (SP) in myocardial ischemia is well understood, but its effects on congestive heart failure are unclear. The present study aimed to use in vitro and in vivo approaches to investigate the effects of SP on doxorubicin‑induced cardiomyocyte injury. Pathological changes, apoptosis, cardiomyocyte ultrastructure and molecular mechanisms were evaluated in vitro and in vivo. The effects of SP on cell viability of H9c2 myocardial cells were evaluated using the Cell Counting Kit‑8 and flow cytometry. B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), Beclin‑1 and microtubule‑associated protein 1A/1B‑light chain 3 (LC3) were detected by western blotting. Heart failure in rats was established by intraperitoneal injection of doxorubicin. The in vitro data demonstrated that SP at concentrations of 1 µg/ml inhibited doxorubicin‑induced apoptosis of H9c2 cells. Administration of doxorubicin reduced Bcl‑2, Beclin‑1 and LC3 expression levels in H9c2 cells, while having no effect on Bax levels. Administration of SP to these doxorubicin‑treated cells did not affect Bcl‑2 or Bax expression, but further reduced Beclin‑1 while inhibiting the reduction in LC3 expression. In vivo, food intake was significantly increased in rats in the SP group compared with the model group. Cardiomyocytes in the heart‑failure group underwent dysfunctional autophagy as ascertained by transmission electron microscopy. Compared with the heart‑failure group, these pathological changes, including loss of striations and vacuolation, were inhibited by SP treatment, which promoted Bax expression, reduced Beclin‑1 expression and inhibited the reduction in LC3 expression. Taken together, SP reduced cardiomyocyte apoptosis in doxorubicin‑induced cardiomyocyte injury, likely by promoting autophagy, which suggested that SP is a potential therapeutic target for doxorubicin‑induced heart failure.
研究领域:
药理学
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心脏病学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 2
·483
·
IF 4.2
Linlin Cui,Li Zhao,Guanghuan Shen,Dahai Yu,Tian Yuan,Yingyu Zhang,Bo Yang
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a–4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound4ashowed the most obvious inhibitory effect on MCF7 cells with an IC50value of 27.57 ± 0.52 μM, which was much lower than cordycepin. Compound4ashowed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound4apromoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound4acould down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound4ainduced the apoptosis of MCF7 cells through the mitochondrial pathway.Keywords:cordycepin derivatives;antitumor;structural modification
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Jingru Zheng,Yuanhong Gao,Jie Ding,Na Sun,Songyi Lin
The study aims to investigate the repair effects of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) and Ser-Asn-Val-Phe-Asp-Met-Phe (SNVFDMF) peptides on scopolamine-caused memory impairment in mice. Behavioral experiments have revealed that Antarctic krill peptides can ameliorate scopolamine caused memory impairment by changing the behavior of mice. In comparison with the scopolamine group, the two peptides at a dose of 40 mg/kg could improve memory impairment. The serum SOD activity (82.82 ± 0.19 vs 79.47 ± 2.42 U/mg prot) and hippocampal ACh level (101.46 ± 3.23 vs 99.85 ± 7.13 μg/mg prot) of SSDAFFPFR were higher than those of SNVFDMF. Hippocampal AChE activity (0.20 ± 0.03 vs 0.53 ± 0.02 U/mg prot), hippocampal MDA level (1.56 ± 0.01 vs 1.63 ± 0.05 nmol/mg prot) and the serum MDA level (3.38 ± 0.24 vs 3.88 ± 0.21 nmol/mg prot) was lower than that of SNVFDMF. The state of mouse hippocampal cells was further observed by a microscopic imaging system. In addition, western blot analysis showed that SSDAFFPFR could significantly inhibit the expression of Bax, caspase-3, and p53, and promote the expression of BCL-XL, CREB, and BDNF, thus protecting hippocampal neurons in mice. In conclusion, the Antarctic krill peptide can repair scopolamine-induced memory impairment in mice.
研究领域:
神经科学
·
药理学
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生物化学
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产品关联
DOI
高影响因子
Frontiers in Chemistry
·
2025
·
IF 4.2
Zhihong Hu,Xixi Hou,Yongjing Ren,Ziyuan Wu,Dong Yan,Hong Chen,Lan Wang
Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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